It is known that cell-extracellular matrix adhesion is involved in various functions such as cell survival, motility and the like. This is a process essential for controlling the normal development of individual, maintenance of tissues, or recovery from damage or infection. An abnormality in the signaling pathway based on such cell adhesion sometimes leads to abnormal development, circulatory diseases or transformation or metastasis of the cells.
In addition, it has been reported that when the cell-extracellular matrix adhesion is inhibited, the cells reach cell death called “anoikis”, and therefore, adhesion to an extracellular matrix is important for the survival of the cells (see non-patent document 1).
Lacritin is a protein identified as a tear secretion promoting factor or a growth-factor-like protein (see patent documents 1 and 2 and non-patent document 2). For lacritin, the following 1) to 5) are reported:
1) Lacritin has an activity as a growth factor for a corneal epithelial cell and a lacrimal gland acinar cell.
2) Lacritin shows a promoting effect on tear protein secretion.
3) Lacritin is expressed in a cell derived from tissues such as the lacrimal gland, parotid gland, minor salivary gland, submandibular gland, thyroid gland, mammary gland and corneal epithelium.
4) Eye drops containing lacritin are likely to be useful in the treatment of ocular diseases such as dry eye syndrome, Sjogren's syndrome, and corneal epithelial wounds.
5) Compounds that bind to lacritin or lacritin receptors can be screened for using a cell expressing a lacritin receptor with a lacritin-dependent calcium signal as an index.
In addition, it has been reported that lacritin or a peptide thereof partly defective in the both terminals has an action to promote division of salivary gland cells in a detection test of 3H-thymidine uptake (see non-patent document 3).
However, it has not been reported that lacritin or a fragment thereof (partial peptide) is involved in adhesion between a cell and extracellular matrix adhesion.
On the other hand, it is known that polypeptide generally having glutamine or glutamic acid on the N-terminal is sometimes unstable in an aqueous solution. As a stabilization method, pyro-modification and the like, namely, a method including synthesis of pyroglutamic acid derivative and the like, are known. However, pyro-modification and the like has been reported to impair inherent activity (patent document 3).    patent document 1: WO02/065943    patent document 2: WO05/119899    patent document 3: JP-A-2003-528112    non-patent document 1: Frisch, S. M. et al., Journal of Cell Biology 124, pp. 619-626 (1994)    non-patent document 2: Sanghi, S. et al., Journal of Molecular Biology 310, pp. 127-139 (2001)    non-patent document 3: Wang, J. et al. Journal of Cell Biology 174, pp. 689-700 (2006)